Morgado, Patrícia I.Jose, SílviaWanke, RiccardoAntunes, Alexandra M.M.Sofia Cardoso, AnaJordao, Luisa2018-02-122018-09-092017-12Environ Toxicol Chem. 2017 Dec;36(12):3404-3414. doi: 10.1002/etc.3927. Epub 2017 Sep 8.730-7268http://hdl.handle.net/10400.18/4936Polycyclic aromatic hydrocarbons (PAHs) are persistent pollutants present in the environment with known mutagenic and carcinogenic properties. In the present study the effect of exposure to single or multiple doses of benzo[a]anthracene (BaA), pyrene (Pyr) and three halogenated derivatives of these compounds (1-ClPyr; 1-BrPyr and 7-ClBaA) were evaluated in a liver-derived human cell line (HepG2). Cytotoxicity as assessed by the classic MTT and neutral red assays showed a mild toxic effect in response to single or multiple dose exposure for up to 72h; except for multiple dose exposure to BaA and 7-ClBaA (1μM per day during 4 days) and single exposure to 10 μM BaA. Furthermore, selective mitochondrial and lysosomal toxicity was observed for Pyr and BaA series, respectively. In order to understand the underlying molecular mechanisms responsible for this effect ROS production, mitochondrial membrane depolarization, lysosomal pH, DNA fragmentation, early and late apoptosis mediators were evaluated after exposure to single doses of the compounds. All compounds were able to trigger oxidative stress after 24h as measured by catalase activity and a good correlation was found between mitochondrial membrane depolarization, lysosomal pH increase and MTT and neutral red assays, respectively. The evaluation of cell death mediators showed that caspase-3/7 but not annexin-V pathways were involved in toxicity triggered by the studied compounds. The integration of all results showed that 1-BrPyr and BaA have a higher toxicity potential.engPolycyclic Aromatic Hydrocarbons (PAHs)CytotoxicityBioaccumulationOrganic ContaminantsToxic EffectsWater DisinfectionProgrammed Cell DeathGenotoxicidade Ambientaljournal article10.1002/etc.3927